During the course of lung injury induced by high oxygen, infection, or trauma, fibroblasts and Type ll epithelial cells undergo a hyperplastic response, and this condition is associated with increased collagen production, fibrosis, and a deteriorating physiology. In recent work we have made two observations which may be important in studying this condition. First, pulmonary surfactant recovered from oxidant-injured animals, in the reparative (hyperplastic) phase of injury, has abnormal physical and chemical properties, and would not be expected to provide alveolar stability. These changes in surfactant are likely to be due, at least in part, to metabolic changes in Type II cells in repair, and are not secondary to fluid transudation exclusively. Second, lung fibroblasts obtained from hamsters or baboons exposed to 100% O2 for 6 days release a factor(s) in conditioned medium which induces accelerated cell replication of normoxic lung fibroblasts. The results of preliminary experiments suggest that it exerts similar effects on Type II cells in primary culture. It is possible, therefore, that during injury to the lung, fibroblast populations arise which secrete an autocrine factor, which induces fibroblast hyperplasia and increased collagen production; and a paracrine factor acting on Type II cells, which results in abnormal surfactant metabolism. These experiments will study the effects on lung cell populations in order to better understand how it may be involved in lung injury. The Specific Aims of the proposal are: 1. To isolate and characterize the factor(s). 2. To study its effects on Type II cells. 3. To investigate certain aspects of cellular mechanism of action. 4. To explore the effects of other growth factors produced by alveolar macrophages on the epithelial-mesenchymal interactions. 5. To study the transcription and translation of this factor, using the techniques of molecular cloning.